Terpyridine Diphosphine Ruthenium Complexes as Efficient Photocatalysts for the Transfer Hydrogenation of Carbonyl Compounds

Abstract The cationic achiral and chiral terpyridine diphosphine ruthenium complexes [RuCl(PP)(tpy)]Cl (PP=dppp (1), (R,R)‐Skewphos (2) and (S,S)‐Skewphos (3)) are easily obtained in 85–88 % yield through a one‐pot synthesis from [RuCl2(PPh3)3], the diphosphine and 2,2′:6′,2′′‐terpyridine (tpy) in 1‐butanol. Treatment of 1–3 with NaPF6 in methanol at RT affords quantitatively the corresponding derivatives [RuCl(PP)(tpy)]PF6 (PP=dppp (1 a), (R,R)‐Skewphos (2 a) and (S,S)‐Skewphos (3 a)). Reaction of [RuCl2(PPh3)3] with (S,R)‐Josiphos or (R)‐BINAP in toluene, followed by treatment with tpy in 1‐butanol and finally with NaPF6 in MeOH gives [RuCl(PP)(tpy)]PF6 (PP=(S,R)‐Josiphos (4 a), (R)‐BINAP (5 a)) isolated in 78 % and 86 % yield, respectively. The chiral derivatives have been isolated as single stereoisomers and 3 a, 4 a have been characterized by single crystal X‐ray diffraction studies. The tpy complexes with NaOiPr display high photocatalytic activity in the transfer hydrogenation (TH) of carbonyl compounds using 2‐propanol as the only hydrogen donor and visible light at 30 °C, at remarkably high S/C (up to 5000) and TOF values up to 264 h−1. The chiral enantiomers 2, 2 a and 3, 3 a induce the asymmetric photocatalytic TH of acetophenone, affording (S)‐ and (R)‐1‐phenylethanol with 51 and 52 % ee, respectively, in a MeOH/2‐propanol mixture.


Introduction
In the recent decades, visible-light photocatalysis has become a valuable powerful tool for the synthesis of organic compounds via active radicals and radical ions, providing access to new molecular transformations, which cannot be achieved under thermal conditions. [1] Transition-metal complexes have been successfully employed in photocatalytic organic synthesis and particular attention has been devoted to ruthenium and iridium photosensitizers. [2] Thus, [Ru(bpy) 3 ]X 2 and [Ir(ppy) 3À n (bpy) n ]X n (n = 0, 1; ppy = 2-phenylpyridine; bpy = 2,2'-bipyridine) type complexes have been used in a number of organic transformations, on account their favorable physical properties (i.e. long excited-state lifetime, high luminescent efficiency). [3] Mono and polynuclear ruthenium complexes based on polypyridine ligands have been extensively investigated in electron-and energy-transfer processes. [4] In this context, the non-innocent redox-active terpyridine (tpy) ligand has been used to obtain robust pincer complexes for catalysis and supramolecular chemistry. [5] Although the [Ru(tpy) 2 ]X 2 species show reduced photophysical properties compared to the related bpy derivatives, on account of the rigidity and narrow bite angle of the NNN ligand, [6] monodentate phosphines tpy complexes show attractive properties as near-infrared sensitizers. [7] In addition to the use of a photosensitizer as single species or in combination with an additional catalyst (dual photoredox catalysis), a transition metal complex may also play a double role by harvesting photon energy and catalyzing bond breaking/ forming reactions via a traditional or a new type of mechanism, avoiding the employment of an exogenous photosensitizer (visible light-induced transition metal catalysis). [8] Despite the extensive use of [Ru(bpy) 3 ] 2 + in photoredox CÀ C coupling reactions, [9] only a few examples of visible light-induced ruthenium catalysts have been recently reported by Ackermann and Greaney, affording the functionalization of heteroarenes. [10] Ruthenium complexes have been efficiently employed in CÀ C and CÀ H forming reactions via thermal homogenous catalysis. The transfer hydrogenation (TH) [11] of carbonyl compounds is a widely accepted method in industry for the production of alcohols, using 2-propanol or formic acid as reducing agents. [12] This highly selective and atom economy process, compared to the classical one with NaBH 4 or LiAlH 4 , makes TH a sustainable transformation in organic synthesis. Highly efficient catalysts are the arene amino [RuCl(arene)(NN)] [13] developed by Noyori, the ampy-type cis-[RuCl 2 (ampy)(PP)] [14] (ampy = 2-aminomethylpyridine), including the pincer [RuCl(CNN)(PP)], [15] [RuCl(CNN)(PPh 3 )(CO)] [16] complexes which also display catalytic activity in related CÀ H activation reactions. [17] On the other hand, the pincer tpy complexes [RuCl n (tpy)(PPh 3 ) 3À n ]X 2À n [18] (n = 1, 2) show moderate catalytic activity in TH, while the diphosphine derivatives [RuY(tpy)(PP)]X and [Ru(L)(tpy)(PP)]X 2 (PP = dppbz, dmpe) [19] have not been investigated in catalysis.
Replacement of the counterion does not cause any significant changes in the 31 P{ 1 H} NMR resonances, whereas the terpyridine H3'/H5' and H3/H3" proton signals of 1 a overlap with the phenyl ones. Similarly to 1, treatment of [RuCl 2 (PPh 3 ) 3 ] with an equimolar amount of (R,R)-Skewphos in 1-butanol at 90°C for 4 h, and subsequent reaction with tpy (1 equiv.) at reflux for 12 h, afforded the single stereoisomer [RuCl((R,R)-Skewphos)(tpy)]Cl (2) as a red product, isolated in 88 % yield (Scheme 1). Complex 2 displays in the 31 P{ 1 H} NMR spectrum two doublets at δ = 49.3 and 33.9 ppm ( 2 J(P,P) = 38.5 Hz) for the P atoms trans to Cl and N atoms, respectively, as established through the long range 4 J(H,P) coupling between the terminal ortho H6 and H6" of tpy (at δ H = 8.83 and 6.63 ppm) and the P trans to N ( 31 P-1 H HMBC 2D NMR experiment, Figure S14). While the H6 resonance is slightly deshielded with respect to the free tpy, the H6" signal is strongly upfield (Δδ = 2.06 ppm), on account of the interaction with a phenyl of the Skewphos, showing a NOE with the ortho phenyl protons at δ = 6.29 ppm ( Figure S15). In addition, the CHCH 3 moiety linked to the P trans to the chloride gives two signals at δ = 2.55 and 0.63 ppm for CH and CH 3 groups, while the resonances at δ = 3.78 and 1.44 ppm are for the other CHCH 3 unity, respectively. As for 1 a, reaction of 2 with an excess of NaPF 6 (2.5 equiv.) in methanol at RT led to the complex [RuCl((R,R)-Skewphos)(tpy)]PF 6 (2 a) in quantitative yield. By using (S,S)-Skewphos, in place of (R,R)-Skewphos and following the same procedures for the synthesis of 2 and 2 a, the corresponding enantiomers 3 and 3 a have been isolated in 85 and 95 % yield. The molecular structure of 3 a has been confirmed by a single crystal X-ray diffraction experiment, which allows to identify the stereochemistry at the ruthenium center ( Figure 1).
Finally, the cationic derivatives [RuCl((S,R)-Josiphos)(tpy)]PF 6 (4 a) and [RuCl((R)-BINAP)(tpy)]PF 6 (5 a) have been obtained through a one-pot reaction from [RuCl 2 (PPh 3 ) 3 ] and the corresponding chiral diphosphine, followed by treatment with tpy in 1-butanol at reflux, giving the chloride complexes 4 and 5 which have been characterized in solution by NMR spectroscopy (see experimental part). Addition of NaPF 6 allow the precipitation of 4 a and 5 a in pure form as single stereoisomers in 78 and 86 % yield, respectively, (Scheme 1). The 31 P{ 1 H} NMR spectrum of 4 a and 5 a give two doublets at δ = 47.6 and 29.0 ppm ( 2 J(P,P) = 35.0 Hz) and two very close doublets at δ = 40.6 and 39.5 ppm ( 2 J(P,P) = 30.3 Hz), respectively. For 4 a, the terminal H6 pyridine proton is downfield shifted at δ H = 9.42 ppm, whereas the corresponding H6" is upfield at δ H = 6.41 ppm due the anisotropic shielding of a diphosphine cyclohexyl rings showing a methylene proton upfield shifted at δ H = À 0.10 ppm. The interaction of a cyclohexyl ring with the tpy has been evidenced also by the crystal structure of 4 a, showing that the tpy plane is slightly tilted out of the equatorial plane due to the steric hindrance of a Cy group ( Figure 2).

Photocatalytic TH of carbonyl compounds promoted by terpyridine ruthenium complexes
The catalytic activity of the pincer complexes 1-3 and 2 a-5 a has been investigated in the TH of ketones and aldehydes to alcohols under light irradiation with a solar simulator (300 W Figure 1. ORTEP style plot of compound 3 a in the solid state (CCDC 2165467). Ellipsoids are drawn at the 50 % probability level. Hydrogen atoms, co-crystallized solvent molecules, and the PF 6 counterion are omitted, and phenyl groups are simplified as wireframes for clarity.  (CCDC 2165468). Ellipsoids are drawn at the 50 % probability level. Hydrogen atoms, co-crystallized solvent molecules, and the PF 6 counterion are omitted, and phenyl groups are simplified as wireframes for clarity. Xenon Arc Lamp). Interestingly, the tpy ruthenium derivatives are found active at remarkably high S/C up to 5000 with 2propanol as the only hydrogen donor and without the use of sacrificial reductants (e.g. triethanolamine) or photosensitizers (Scheme 2). In addition, asymmetric photocatalytic TH of acetophenone a has been observed with the chiral pincer derivatives in 2-propanol/MeOH mixtures.
By using 2, bearing (R,R)-Skewphos, a complete reduction of a occurs in 8 h, with TOF of 148 h À 1 , affording the alcohol as racemic mixture (entry 2) and much of the same activity has been observed with 2 a, indicating that the type of counterions (Cl À vs. PF 6 À ) does not affect the photocatalysis (entry 3). Interestingly, 2 catalyzes the TH of a at S/C = 5000, with 86 % conversion in 24 h and high TOF = 205 h À 1 (entry 4). A decrease of rate has been observed for different amounts of NaOiPr (1, 5 and 10 mol %) (entries 5-7) with respect to 2 mol %, whereas no photocatalysis occurs in the absence of the base.
The ee values of the S and R alcohols are much the same, within the experimental error, and are consistent with the use of enantiomer catalysts. The derivatives 4 a and 5 a, bearing the diphosphine (S,R)-Josiphos and (R)-BINAP, respectively, lead to 95 and 98 % photocatalytic conversion of a in 14 h with TOF = 94 and 88 h À 1 , respectively (entries 14 and 16), whereas using a MeOH/2-propanol (1/1) mixture, leads to poor chiral induction (14 and 18 % ee of the S alcohol; entries 15 and 17). The comparison of the TH catalyzed by the pincer 4 a in MeOH/2propanol (upon irradiation) with [RuCl(CNN)(S,R)-Josiphos)] [34] in 2-propanol (under thermal conditions) containing the same diphosphine, affords the S alcohol as predominant enantiomer. Conversely, 3 and 3 a afford the R enantiomer, while the corresponding [RuCl(CNN)(S,S)-Skewphos)] derivatives [35] give the S one. A mercury poisoning test [36] carried out with 2 shows the same performance, suggesting that the catalysis occurs in homogeneous phase (entry 18). It is worth pointing out that no decrease of the enantioselectivity or deactivation of the ruthenium catalyst has been observed during irradiation. To the best of our knowledge, this is the first example of an asymmetric TH of a ketone promoted by light. A solvent effect Scheme 2. TH of carbonyl compounds photocatalyzed by terpyridine ruthenium complexes. on the catalytic asymmetric hydrogenation of C=O and C=N bonds has been previously reported, [37] leading in same cases to a reversal of enantioselectivity. [37b] Thus, the influence of methanol suggests that the asymmetric catalysis occurs within the chiral environment of the photocatalyst, possibly through π-stacking interactions between the tpy rings and the phenyl ring of the substrate, [38] favored by the hydrogen bonding of methanol vs. 2-propanol media. Notably, the well-known photosensitizer [Ru(bpy) 3 ](PF 6 ) 2 has been shown to photocatalyze the TH of a leading to incomplete reduction (61 % conv.) in 8 h at 30°C and with a TOF of 73 h À 1 under the same catalytic conditions (entry 19).
To enlarge the scope of the photocatalytic TH, the NNN pincer complexes have been studied in the reduction of (bulky) ketones and aldehydes following the optimized protocol. Thus, 1 photocatalyzes the complete reduction of benzophenone b to benzhydrol at S/C = 1000 after 12 h of irradiation, with a TOF = 115 h À 1 (entry 1, Table 2). With 2 at S/C = 1000 and 5000, the reaction occurs faster with 99 % and 95 % conversions in 6 and 22 h and TOF up to 264 h À 1 , respectively (entries 2 and 3). Complex 1 catalyzes the TH of cyclohexanone c to cyclohexanol (91 % conv.) at S/C = 1000 in 18 h (TOF = 82 h À 1 , entry 4), while with 2 at S/C = 1000 and 5000, c is quantitatively reduced in 8 and 25 h, respectively (TOF up to 207 h À 1 ; entries 5, 6). The (S,R)-Josiphos derivative 4 a affords 99 % conversion of c in 21 h at S/ C = 500 (entries 7). The aldehyde 4-bromo-benzaldehyde d is reduced with 1 (S/C = 1000) to the corresponding alcohol (88 % conv.) in 21 h, whereas with 2 quantitative reduction occurs within a shorter time frame (18 h) (entries 8, 9).

Photocatalytic TH studies promoted by terpyridine ruthenium complexes
To confirm the catalytic light-driven process, control experiments have been carried out with the pincer complexes under alternating light and dark conditions. Upon irradiation, the conversion of a to 1-phenylethanol with 2 (S/C = 5000) in 2propanol at 30°C increases linearly, while in the dark the alcohol is formed in tiny amount (< 1%), resulting in a clear "on/off" process and indicating that the pincer photocatalyst is active for days ( Figure 3).
After an induction period of about 15 min in which the color of the reaction mixture changes from orange to dark purple and finally to light yellow under light ( Figure S39 in the Supporting Information), the reduction of a with 2 (S/C = 1000) follows a zero order kinetic till about 80 % conversion and with complete formation of 1-phenylethanol in 8 h. Conversely, in the dark at 30°C the conversion is less than 2 % while at refluxing conditions (82°C) only 11 % of alcohol is formed in 8 h ( Figure 4).
To shed light on the steps involved in the photocatalysis, NMR studies have been carried out on the single reactions. Treatment of 2 with NaOiPr (3 equiv.) in 2-propanol-d 8 at room temperature in the dark leads to a tiny amount of the ruthenium isopropoxide [Ru(OiPr)((R,R)-Skewphos)(tpy)](OiPr) (A) species ( Figure S45). Upon irradiation (30 min.) the complex A forms quantitatively through photo-displacement of the chloride and has been characterized by NMR in solution (Scheme 3 and Figure S46-S49).
The alkoxide A shows two doublets at δ P = 50.5 and 38.4 ppm ( 2 J(P,P) = 35.2 Hz) for the P atoms trans to the O and N atoms, whereas the terminal tpy H6 and H6" resonances are at δ H = 8.80 and 6.70 ppm. In addition, the CH and CH 3 signals of the RuOiPr moiety are at δ H = 3.93, 1.14 ppm and δ C = 63.1 and 25.3 ppm, respectively, as inferred from 1 H-13 C HSQC NMR measurements ( Figure S50-S51). After a longer irradiation period (> 2 h) the red-orange solution of A turns dark brown, affording the ruthenium hydride [RuH((R,R)-Skewphos)(tpy)](OiPr) (B), through a light-induced β-hydrogen elimination with extrusion of acetone, in the presence of uncharacterized species (Scheme 3). The 1 H NMR spectrum of B reveals a doublet of doublets at δ = À 7.49 ppm with 2 J(H,P) = 78.2 and 25.3 Hz, for two P atoms trans and cis to the hydride, in agreement with the related CNN pincer ruthenium hydride complexes containing a diphosphine, [39] and the peaks at δ H = 8. 30, 8.27, 8.11 and 7.86 ppm for tpy ligand ( Figure S53-S54). NMR experiments performed in 2-propanol/toluene-d 8 (1/1 in volume) as solvent leads to similar results, with formation of B in lower amount ( Figure S55-S56) and attempts to isolate the hydride B by treatment of 2 with NaOiPr in 2-propanol failed. Reaction of the substrate b (1 equiv.) with B in 2-propanol/ toluene-d 8 (1/1 in volume), followed by irradiation for 1 h, leads to the quantitative conversion to benzhydrol and acetone in the presence of B. Addition of a second equivalent of b give complete reduction after 1 h under light, indicating that the hydride B is involved in the photocatalytic TH ( Figure S57-S58). Finally, irradiation of b with B in 2-propanol-d 8 leads to partial deuteration of benzhydrol at the C α position, via the formation of a RuD species ( Figure S59-S64). Based on these results, it is likely that photocatalytic TH with the pincer complexes involves a light-driven substitution of the chloride with formation of the OiPr derivative A, followed by a β-H-elimination of acetone, a process which is also induced by light (photo-β-H-elimination), leading to ruthenium hydride B. [40] Subsequent reduction of the carbonyl compound under irradiation affords the alkoxide C which is protonated by 2propanol with formation of the alcohol product and the isopropoxide A that closes the cycle (Scheme 3). It is worth noting that under thermal conditions the CÀ H activation of the metal-alkoxides (type A) generally requires a cis vacant site, [41] even though a facile β-hydrogen elimination in 18-electron Ir III complexes through hydrogen bonding with the alcohol media has been claimed by Milstein. [42] Under light irradiation we have found that the 18-electron complex A undergoes a β-hydrogen elimination and that the metal-hydride B is involved in the ketone reduction, possibly through the formation of a Rualkoxide, on account of the microscopic reversibility. The asymmetric TH of a with chiral pincer derivatives (2-5) in methanol/2-propanol can be ascribed to the favorable chiral environment of the photocatalyst possibly by π-stacking interaction of the aromatic rings. The asymmetric TH of acetophenone by pincer ruthenium complexes indicates that this process occurs through a well-defined chiral photocatalyst without dissociation of the NNN and PP ligands. Therefore, this represents a rare example of visible light-induced transition metal catalysis with ruthenium, which combines the catalystsubstrate interaction with the photoinduced processes.

Conclusions
In summary, the cationic terpyridine diphosphine ruthenium complexes [RuCl(diphosphine)(tpy)]X (X = Cl and PF 6 ) have been easily prepared in high yield through a one-pot synthesis from [RuCl 2 (PPh 3 ) 3 ], a diphosphine, terpyridine (tpy) and additional NaPF 6 . By using the chiral diphosphines Skewphos, Josiphos and BINAP, single stereoisomers are formed. The reported tpy ruthenium complexes display high catalytic activity in the transfer hydrogenation (TH) of ketones and aldehydes to alcohols at 30°C induced by light irradiation, using 2-propanol as the only hydrogen donor. These pincer complexes allow a remarkably high S/C up to 5000 and rate (TOFs up to 264 h À 1 ), while poor activity is found under thermal conditions. The chiral complexes [RuCl((R,R)-Skewphos)(tpy)]X (X = Cl and PF 6 ) catalyze the TH of acetophenone in methanol/2-propanol, affording (S)-1-phenylethanol in 52 % ee, while the enantiomers [RuCl((S,S)-Skewphos)(tpy)]X give the R alcohol. This is the first example of asymmetric catalytic TH of a ketone driven by light, indicating that this reaction occurs at a well-defined and robust visible light-induced ruthenium catalyst. For these tpy complexes, photo-dissociation and photo-ß-H-elimination reactions have been observed and are likely to occur during catalysis. Studies are ongoing to rationalize the mechanism of the photocatalytic reduction and to apply these catalysts in other CÀ H activation reactions, including asymmetric transformations under light irradiation.

Experimental Section
General: All reactions were carried out under an argon atmosphere using standard Schlenk techniques. The solvents were carefully dried by standard methods and distilled under argon before use. The ruthenium complex [RuCl 2 (PPh 3 ) 3 ] [43] was prepared according to literature procedures, whereas all other chemicals were purchased from Aldrich and Strem and used without further purification. NMR measurements were recorded on an Avance III HD NMR 400 spectrometer. Chemical shifts (ppm) are relative to TMS for 1 H and 13 C{ 1 H}, whereas H 3 PO 4 was used for 31 P{ 1 H}. The atom-numbering scheme for the NMR assignment of terpyridine ligand in the ruthenium complexes is presented in Figure 5. Elemental analyses (C, H, N) were carried out with a Carlo Erba 1106 analyzer, whereas GC analyses were performed with a Varian CP-3380 gas chromatograph equipped with a 25 m length MEGADEX-ETTBDMS-β chiral column with hydrogen (5 psi) as the carrier gas and flame ionization detector (FID). The injector and detector temperature Scheme 3. Proposed mechanism for the photocatalytic TH of carbonyl compounds promoted by the terpyridine ruthenium complexes. was 250°C, with initial T = 95°C ramped to 140°C at 3°C/min for a total of 20 min of analysis. The t R of acetophenone was 7.59 min, while the t R of (R)-and (S)-1-phenylethanol were 10.49 min and 10.76 min, respectively.
Deposition Numbers 2165467 (for 3 a), 2165468 (for 4 a) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.
Supporting Information available: NMR data of the isolated complexes, x-ray crystallographic details of 3 a and 4 a and further data for the photocatalytic TH of carbonyl compounds promoted by the ruthenium derivatives.